What’s New in Acute Lymphocytic Leukemia Research and Treatment?

Researchers are now studying the causes, diagnosis, supportive care, and treatment of acute lymphocytic leukemia (ALL) at many medical centers, university hospitals, and other institutions.

Genetics of leukemia

Scientists are making great progress in understanding how changes in a person’s DNA can cause normal bone marrow cells to develop into leukemia cells. A greater understanding of the genes (regions of the DNA) involved in certain translocations that often occur in ALL is providing insight into why these cells become abnormal. Doctors are now looking to learn how to use these changes to help them determine a person’s outlook and whether they should receive more or less intensive treatment.

As this information unfolds, it may also be used to develop newer targeted therapies against ALL. Drugs such as imatinib (Gleevec) and dasatinib (Sprycel) are examples of such treatments. They are now used in treating ALL patients whose leukemia cells have the Philadelphia chromosome.

Gene expression profiling

This new lab technique is being studied to help identify and classify different cancers. Instead of looking at single genes, this test uses a special technology to look at the patterns of many different genes in the cancer cells at the same time. This may add to the information that comes from the current lab tests.

This information may eventually allow more personalized treatment by predicting which chemo drugs are likely to be most effective for each patient. These tests are also being used to find previously unknown changes inside ALL cells to help guide researchers in developing new drugs.

Detecting minimal residual disease

Progress in understanding DNA changes in ALL has already provided a highly sensitive test for detecting minimal residual disease after treatment – when so few leukemia cells are present that they cannot be found by routine bone marrow tests.

The polymerase chain reaction (PCR) test can identify ALL cells based on their gene translocations or rearrangements. This test can find one leukemia cell among many thousands of normal cells. A PCR test can be used in determining how completely chemotherapy has destroyed the ALL cells.

Doctors are now trying to determine if patients with minimal residual disease will benefit from further or more intensive treatment.

Improving chemotherapy

Studies are in progress to find the most effective combination of chemotherapy (chemo) drugs while limiting unwanted side effects. This is especially important in older patients, who often have a harder time tolerating current treatments.

New chemo drugs are also being developed and tested. For example, clofarabine (Clolar®) is approved to treat childhood ALL and shows promise in early studies of adults with this disease. Many other new drugs are also being studied.

Studies are also under way to determine whether patients with certain unfavorable prognostic features benefit from more intensive chemo, and whether some ALL patients with favorable prognostic factors might not need as much treatment.

The effectiveness of chemotherapy may be limited in some cases because the leukemia cells become resistant to it. Researchers are now looking at ways to prevent or reverse this resistance by using other drugs along with chemotherapy.

Stem cell transplants

Researchers continue to refine stem cell transplants to try to increase their effectiveness, reduce complications and determine which patients are likely to be helped by this treatment. Many studies are being done to try to help determine exactly when allogeneic, autologous, and mini-transplants might best be used.

Doctors are also studying donor leukocyte infusion in people who have already received an allogeneic transplant and who relapse. In this technique, the patient gets an infusion of white blood cells (leukocytes) from the same donor who contributed stem cells for the original transplant. The hope is that the cells will boost the new immune system and add to the graft-versus-leukemia effect. Early study results have been promising, but more research on this approach is needed.

Monoclonal antibodies

These drugs are man-made versions of immune system proteins (antibodies). They can be targeted to attach only to certain molecules, such as proteins on the surface of certain lymphocytes.

Some monoclonal antibodies, such as rituximab (Rituxan) and alemtuzumab (Campath), are already used to treat other blood disorders and are now being studied for use against ALL. Early results have been favorable, but it is still too early to know for sure.

Epratuzumab, a newer antibody, has also shown promise against ALL in early studies. Further studies are planned.

Another approach is to attach a chemo drug to a monoclonal antibody. The antibody serves as a homing device to bring the chemo drug to the cancer cell. One such drug, inotuzumab ozogamicin, has shown promise in treating ALL.

Studies of several other monoclonal antibodies to treat ALL are now under way as well.

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